Induction of lnterieukin-12/p40 by superantigens in macrophages is mediated by activation of nuclear factor-κB

Multimerization of the MHC class II molecule by superantigens results in activation of cellular signal transduction pathways in macrophage and B cells. Here we show that superantigen staphylococcal enterotoxin B (SEB) induces IL-12/p40 secretion in macrophages. SEE-induced expression of the IL-12/p40 gene involves activation and nuclear translocation of nuclear factor kappa B (NF-kappa B). The NF-kappa B heterodimer bound to the NF-kappa B consensus sequence of the IL-12/p40 gene promoter is p50/C-Rel. Inhibition of PHC and PKA activation results in suppression of activation and translocation of NF-kappa B. We conclude that signals for IL-12/p40 gene transcription from MHC class II: molecules follow activation of PKC and PKA, which in turn leads to the activation and translocation of NF-kappa B to the nucleus. Our study suggests that superantigens are capable of influencing the nature of the immune response by regulating cytokine production. Induction of IL-12 production by superantigens may therefore play a role in the regulation of Th 1-mediated immune response and autoimmune disease. (C) 2000 Academic Press.